Detection of Circulating Tumor Cells in Patients with Breast, Prostate, Pancreatic, Colon and Melanoma Cancer: A Blinded Comparative Study Using Healthy Donors
Author(s)
Ioannis Papasotiriou*,
Marina Chatziioannou,
Konstantina Pessiou,
Ippokratis Retsas,
Georgia Dafouli,
Antigoni Kyriazopoulou,
Maria Toloudi,
Irene Kaliara,
Ioanna Vlachou,
Eleni Kourtidou,
Vasiliki Kipourou,
Evanthia Georgiou,
Dimitrios Athanasios Ntanovasilis,
Christos Theodosiou,
Aikaterini Pantopikou,
Panagiotis Apostolou
ABSTRACT
Cancer is a diverse disease characterized by abnormal cell growth and the ability to invade or spread to other parts of the body. Because the yearly cancer rate is increasing, an important area for cancer researchers is to improve the ability to detect and treat cancer early. The current study analyzes the potential of flow cytometry to be used to detect circulating tumor cells (CTCs) in patients with various cancer types and stages. CTCs are cells that have detached from the primary tumor and entered the blood stream in the process of metastasizing to other organs. To determine the accuracy of flow cytometry in detecting CTCs, a comparative study was performed on healthy donors. In this study, blood samples from patients with breast, prostate, pancreatic, colon and skin cancer were analyzed and compared with healthy donors. The data were collected and analyzed statistically with receiver operating characteristic curve analysis. The results indicate that CTCs can be detected in over 83% of the cancer patients and therefore may be a promising method for diagnosing cancer.
Cancer is a diverse disease characterized by abnormal cell growth and the ability to invade or spread to other parts of the body. Because the yearly cancer rate is increasing, an important area for cancer researchers is to improve the ability to detect and treat cancer early. The current study analyzes the potential of flow cytometry to be used to detect circulating tumor cells (CTCs) in patients with various cancer types and stages. CTCs are cells that have detached from the primary tumor and entered the blood stream in the process of metastasizing to other organs. To determine the accuracy of flow cytometry in detecting CTCs, a comparative study was performed on healthy donors. In this study, blood samples from patients with breast, prostate, pancreatic, colon and skin cancer were analyzed and compared with healthy donors. The data were collected and analyzed statistically with receiver operating characteristic curve analysis. The results indicate that CTCs can be detected in over 83% of the cancer patients and therefore may be a promising method for diagnosing cancer.
Cite this paper
Papasotiriou, I. , Chatziioannou, M. , Pessiou, K. , Retsas, I. , Dafouli, G. , Kyriazopoulou, A. , Toloudi, M. , Kaliara, I. , Vlachou, I. , Kourtidou, E. , Kipourou, V. , Georgiou, E. , Ntanovasilis, D. , Theodosiou, C. , Pantopikou, A. and Apostolou, P. (2015) Detection of Circulating Tumor Cells in Patients with Breast, Prostate, Pancreatic, Colon and Melanoma Cancer: A Blinded Comparative Study Using Healthy Donors. Journal of Cancer Therapy, 6, 543-553. doi: 10.4236/jct.2015.67059.
Papasotiriou, I. , Chatziioannou, M. , Pessiou, K. , Retsas, I. , Dafouli, G. , Kyriazopoulou, A. , Toloudi, M. , Kaliara, I. , Vlachou, I. , Kourtidou, E. , Kipourou, V. , Georgiou, E. , Ntanovasilis, D. , Theodosiou, C. , Pantopikou, A. and Apostolou, P. (2015) Detection of Circulating Tumor Cells in Patients with Breast, Prostate, Pancreatic, Colon and Melanoma Cancer: A Blinded Comparative Study Using Healthy Donors. Journal of Cancer Therapy, 6, 543-553. doi: 10.4236/jct.2015.67059.
References
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http://dx.doi.org/10.1158/2159-8290.CD-12-0558
[1] Siegel, R., Ma, J., Zou, Z. and Jemal, A. (2014) Cancer Statistics, 2014. CA: A Cancer Journal for Clinicians, 64, 9-29.
http://dx.doi.org/10.3322/caac.21208 [2] Chaffer, C.L. and Weinberg, R.A. (2011) A Perspective on Cancer Cell Metastasis. Science, 331, 1559-1564.
http://dx.doi.org/10.1126/science.1203543 [3] Chambers, A.F., Groom, A.C. and MacDonald, I.C. (2002) Dissemination and Growth of Cancer Cells in Metastatic Sites. Nature Reviews Cancer, 2, 563-572.
http://dx.doi.org/10.1038/nrc865 [4] Williams, S.C. (2013) Circulating Tumor Cells. Proceedings of the National Academy of Sciences of the USA, 110, 4861.
http://dx.doi.org/10.1073/pnas.1304186110 [5] Plaks, V., Koopman, C.D. and Werb, Z. (2013) Cancer. Circulating Tumor Cells. Science, 341, 1186-1188.
http://dx.doi.org/10.1126/science.1235226 [6] Miller, M.C., Doyle, G.V. and Terstappen, L.W. (2010) Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer. Journal of Oncology, 2010, Article ID: 617421.
http://dx.doi.org/10.1155/2010/617421 [7] Smirnov, D.A., Zweitzig, D.R., Foulk, B.W., Miller, M.C., Doyle, G.V., Pienta, K.J., Meropol, N.J., Weiner, L.M., Cohen, S.J., Moreno, J.G., et al. (2005) Global Gene Expression Profiling of Circulating Tumor Cells. Cancer Research, 65, 4993-4997.
http://dx.doi.org/10.1158/0008-5472.CAN-04-4330 [8] Stott, S.L., Hsu, C.H., Tsukrov, D.I., Yu, M., Miyamoto, D.T., Waltman, B.A., Rothenberg, S.M., Shah, A.M., Smas, M.E., Korir, G.K., et al. (2010) Isolation of Circulating Tumor Cells Using a Microvortex-Generating Herringbone-Chip. Proceedings of the National Academy of Sciences of the USA, 107, 18392-18397.
http://dx.doi.org/10.1073/pnas.1012539107 [9] Gredelj-Simec, N., Jelic-Puskaric, B., Ostojic, A., Siftar, Z., Fiala, D., Kardum-Skelin, I., Vrhovac, R. and Jaksic, B. (2011) Diagnostic and Prognostic Significance of CD45 Cell Surface Antigen Expression in Hematologic Malignancies with Main Focus on Acute Leukemias. Acta Medica Croatica, 65, 45-52. [10] Liu, L. and Shi, G.P. (2012) CD31: Beyond a Marker for Endothelial Cells. Cardiovascular Research, 94, 3-5.
http://dx.doi.org/10.1093/cvr/cvs108 [11] Sorenson, S.C., Asch, B.B., Connolly, J.L., Burstein, N.A. and Asch, H.L. (1987) Structural Distinctions among Human Breast Epithelial Cells Revealed by the Monclonal Antikeratin Antibodies AE1 and AE3. The Journal of Pathology, 153, 151-162.
http://dx.doi.org/10.1002/path.1711530208 [12] Gentile, A., Trusolino, L. and Comoglio, P.M. (2008) The Met Tyrosine Kinase Receptor in Development and Cancer. Cancer and Metastasis Reviews, 27, 85-94.
http://dx.doi.org/10.1007/s10555-007-9107-6 [13] Hollingsworth, M.A. and Swanson, B.J. (2004) Mucins in Cancer: Protection and Control of the Cell Surface. Nature Reviews Cancer, 4, 45-60.
http://dx.doi.org/10.1038/nrc1251 [14] Maria, T., Panagiotis, A., Marina, C., Eleni, K., Ioanna, V., Georgia, M. and Ioannis, P. (2014) How Prostate-Specific Membrane Antigen Level May Be Correlated with Stemness in Prostate Cancer Stem Cell-Like Cell Populations? Journal of Cancer Research and Therapeutics, 10, 133-141.
http://dx.doi.org/10.4103/0973-1482.131461 [15] Radford, K.J., Thorne, R.F. and Hersey, P. (1996) CD63 Associates with Transmembrane 4 Superfamily Members, CD9 and CD81, and with Beta 1 Integrins in Human Melanoma. Biochemical and Biophysical Research Communications, 222, 13-18.
http://dx.doi.org/10.1006/bbrc.1996.0690 [16] Linden, A. (2006) Measuring Diagnostic and Predictive Accuracy in Disease Management: An Introduction to Receiver Operating Characteristic (ROC) Analysis. Journal of Evaluation in Clinical Practice, 12, 132-139.
http://dx.doi.org/10.1111/j.1365-2753.2005.00598.x [17] Mitchell, P.S., Parkin, R.K., Kroh, E.M., Fritz, B.R., Wyman, S.K., Pogosova-Agadjanyan, E.L., Peterson, A., Noteboom, J., O’Briant, K.C., Allen, A., et al. (2008) Circulating microRNAs as Stable Blood-Based Markers for Cancer Detection. Proceedings of the National Academy of Sciences of the United States of America, 105, 10513-10518.
http://dx.doi.org/10.1073/pnas.0804549105 [18] Toloudi, M., Apostolou, P., Chatziioannou, M. and Papasotiriou, I. (2011) Correlation between Cancer Stem Cells and Circulating Tumor Cells and Their Value. Case Reports in Oncology, 4, 44-54.
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http://dx.doi.org/10.1080/20014091084218 [21] Tibbe, A.G., Miller, M.C. and Terstappen, L.W. (2007) Statistical Considerations for Enumeration of Circulating Tumor Cells. Cytometry Part A, 71, 154-162.
http://dx.doi.org/10.1002/cyto.a.20369 [22] Hermann, P.C., Huber, S.L., Herrler, T., Aicher, A., Ellwart, J.W., Guba, M., Bruns, C.J. and Heeschen, C. (2007) Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer. Cell Stem Cell, 1, 313-323.
http://dx.doi.org/10.1016/j.stem.2007.06.002 [23] Kalluri, R. and Weinberg, R.A. (2009) The Basics of Epithelial-Mesenchymal Transition. Journal of Clinical Investigation, 119, 1420-1428.
http://dx.doi.org/10.1172/JCI39104 [24] Mani, S.A., Guo, W., Liao, M.J., Eaton, E.N., Ayyanan, A., Zhou, A.Y., Brooks, M., Reinhard, F., Zhang, C.C., Shipitsin, M., et al. (2008) The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells. Cell, 133, 704-715.
http://dx.doi.org/10.1016/j.cell.2008.03.027 [25] Riethdorf, S., Fritsche, H., Muller, V., Rau, T., Schindlbeck, C., Rack, B., Janni, W., Coith, C., Beck, K., Janicke, F., et al. (2007) Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Metastatic Breast Cancer: A Validation Study of the Cell Search System. Clinical Cancer Research, 13, 920-928.
http://dx.doi.org/10.1158/1078-0432.CCR-06-1695 [26] Marrinucci, D., Bethel, K., Lazar, D., Fisher, J., Huynh, E., Clark, P., Bruce, R., Nieva, J. and Kuhn, P. (2010) Cytomorphology of Circulating Colorectal Tumor Cells: A Small Case Series. Journal of Oncology, 2010, Article ID: 861341.
http://dx.doi.org/10.1155/2010/861341 [27] Meng, S., Tripathy, D., Frenkel, E.P., Shete, S., Naftalis, E.Z., Huth, J.F., Beitsch, P.D., Leitch, M., Hoover, S., Euhus, D., et al. (2004) Circulating Tumor Cells in Patients with Breast Cancer Dormancy. Clinical Cancer Research, 10, 8152-8162.
http://dx.doi.org/10.1158/1078-0432.CCR-04-1110 [28] Allard, W.J., Matera, J., Miller, M.C., Repollet, M., Connelly, M.C., Rao, C., Tibbe, A.G., Uhr, J.W. and Terstappen, L.W. (2004) Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but Not in Healthy Subjects or Patients with Nonmalignant Diseases. Clinical Cancer Research, 10, 6897-6904.
http://dx.doi.org/10.1158/1078-0432.CCR-04-0378 [29] Momburg, F., Moldenhauer, G., Hammerling, G.J. and Moller, P. (1987) Immunohistochemical Study of the Expression of a Mr 34,000 Human Epithelium-Specific Surface Glycoprotein in Normal and Malignant Tissues. Cancer Research, 47, 2883-2891. [30] Pachmann, K., Camara, O., Kavallaris, A., Krauspe, S., Malarski, N., Gajda, M., Kroll, T., Jorke, C., Hammer, U., Altendorf-Hofmann, A., et al. (2008) Monitoring the Response of Circulating Epithelial Tumor Cells to Adjuvant Chemotherapy in Breast Cancer Allows Detection of Patients at Risk of Early Relapse. Journal of Clinical Oncology, 26, 1208-1215.
http://dx.doi.org/10.1200/JCO.2007.13.6523 [31] Cristofanilli, M. (2009) The Biological Information Obtainable from Circulating Tumor Cells. The Breast, 18, S38-S40.
http://dx.doi.org/10.1016/s0960-9776(09)70270-x [32] Sterzynska, K., Kempisty, B., Zawierucha, P. and Zabel, M. (2012) Analysis of the Specificity and Selectivity of Anti-EpCAM Antibodies in Breast Cancer Cell Lines. Folia Histochemica et Cytobiologica, 50, 534-541.
http://dx.doi.org/10.5603/FHC.2012.0075 [33] Moncada, D.M., Kammanadiminti, S.J. and Chadee, K. (2003) Mucin and Toll-Like Receptors in Host Defense against Intestinal Parasites. Trends in Parasitology, 19, 305-311.
http://dx.doi.org/10.1016/S1471-4922(03)00122-3 [34] Wang, M.X., Earley Jr., J.J., Shields, J.A. and Donoso, L.A. (1992) An Ocular Melanoma-Associated Antigen. Molecular Characterization. Archives of Ophthalmology, 110, 399-404.
http://dx.doi.org/10.1001/archopht.1992.01080150097036 [35] Iida, J., Skubitz, A.P., McCarthy, J.B. and Skubitz, K.M. (2005) Protein Kinase Activity Is Associated with CD63 in Melanoma Cells. Journal of Translational Medicine, 3, 42.
http://dx.doi.org/10.1186/1479-5876-3-42 [36] O’Keefe, D.S., Bacich, D.J. and Heston, W.D. (2004) Comparative Analysis of Prostate-Specific Membrane Antigen (PSMA) versus a Prostate-Specific Membrane Antigen-Like Gene. Prostate, 58, 200-210.
http://dx.doi.org/10.1002/pros.10319 [37] Bardelli, A., Corso, S., Bertotti, A., Hobor, S., Valtorta, E., Siravegna, G., Sartore-Bianchi, A., Scala, E., Cassingena, A., Zecchin, D., et al. (2013) Amplification of the MET Receptor Drives Resistance to Anti-EGFR Therapies in Colorectal Cancer. Cancer Discovery, 3, 658-673.
http://dx.doi.org/10.1158/2159-8290.CD-12-0558